5-[(9H-Fluoren-9-ylmethoxycarbonylamino)-methyl]-furan-2-carboxylic acid | 503469-51-0

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 5-[(9H-Fluoren-9-ylmethoxycarbonylamino)-methyl]-furan-2-carboxylic acid
• 英文别名: 5-({[(9H-fluoren-9-ylmethoxy)carbonyl]amino}methyl)furan-2-carboxylic acid；5-[(9H-fluoren-9-ylmethoxycarbonylamino)methyl]furan-2-carboxylic acid
• CAS: 503469-51-0
• 化学式: C₂₁H₁₇NO₅
• mdl: MFCD23810403
• 分子量: 363.37
• InChiKey: KRRSDMPUICWCLM-UHFFFAOYSA-N

物化性质

• 沸点：
  616.7±55.0 °C(Predicted)
• 密度：
  1.342±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  27
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.142
• 拓扑面积：
  88.8
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  5-氯磺酰基-2-羟基苯甲酸 、 5-[(9H-Fluoren-9-ylmethoxycarbonylamino)-methyl]-furan-2-carboxylic acid 、 5-(2-chloro-benzylsulfanyl)-3(9H-fluoren-9-ylmethoxycarbonylamino)-4-oxo-pentanoic acid tert-butyl ester 以5.5 mg的产率得到Inhibitor 70b
  参考文献：
  名称：

  Identification of Potent and Selective Small-Molecule Inhibitors of Caspase-3 through the Use of Extended Tethering and Structure-Based Drug Design

  摘要：

  The design, synthesis, and in vitro activities of a series of potent and selective small-molecule inhibitors of caspase-3 are described. From extended tethering, a salicylic acid fragment was identified as having binding affinity for the S-4 pocket of caspase-3. X-ray crystallography and molecular modeling of the initial tethering hit resulted in the synthesis of 4, which reversibly inhibited caspase-3 with a K-i = 40 nM. Further optimization led to the identification of a series of potent and selective inhibitors with K-i values in the 20-50 nM range. One of the most potent compounds in this series, 66b, inhibited caspase-3 with a K-i = 20 nM and selectivity of 8-500-fold for caspase-3 vs a panel of seven caspases (1, 2, and 4-8). A high-resolution X-ray cocrystal structure of 4 and 66b supports the predicted binding modes of our compounds with caspase-3.

  DOI：

  10.1021/jm020230j